Acute Lymphocytic LeukemiaPhase 1/2NCT03076437
Anti-CD19 Chimeric Antigen Receptor (CAR)-Transduced T Cell Therapy for Patients With B Cell Malignancies
A Phase 1/2 study testing Drugs and Anti-CD19-CAR transduced T cells in people with Acute Lymphocytic Leukemia and Chronic Lymphocytic Leukemia, run by Shenzhen Institute for Innovation and Translational Medicine at 1 site in China.
Trial summary
Autologous T cells engineered to express an anti-CD19 chimeric antigen receptor (CAR) will be infused back to patients with B cell malignancies, including lymphoma and leukemia. The patients will be monitored after infusion of anti-CD19 CAR-transduced T cells for adverse events, persistence of anti-CD19 CAR-transduced… Read more about this study
- Who is it for?
- Ages 1 year to 80 years
- Conditions the study is for
- Acute Lymphocytic Leukemia, Chronic Lymphocytic Leukemia, Lymphoma
- What is being tested?
- Drugs and Anti-CD19-CAR transduced T cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteChina
- Study dates
- 15 Jan 2016to 31 Dec 2019
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients must have a CD19+ B cell malignancy，including relapsed or refractory B cell leukemia and B cell lymphoma；
- Patients with CD19+ B cell malignancies are not able to receive standard treatments and willing to participate in the trial;
- Patients must have a measurable or evaluable disease at the time of enrollment, which may include any evidence of disease including minimal residual disease detected by flow cytometry, cytogenetics, or polymerase chain reaction (PCR) analysis；
- patients are not eligible for autologous or allogeneic stem-cell transplantation (SCT) or relapsed after autologous or allogeneic stem-cell transplantation；
- Patients with history of allogeneic stem cell transplantation are eligible, providing 6 months had elapsed from SCT, they have no evidence of active graft-versus-host disease and no longer taking immunosuppressive agents during the treatment.
- Willing to sign a durable power of attorney；
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- Able to understand and sign the Informed Consent Document；
- Performance status：ECOG 0-2；
- Life expectancy：More than 3 months；
- Patients of both genders must be willing to practice birth control for four months after receiving a lymphodepleting preconditioning regimen；
- Female participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion, because of the potentially dangerous effects on the fetus；
- There is no obvious dysfunctions in heart , liver and kidney, and the functions of vital organs are normal；
- Serology： (1) Seronegative for HIV antibody； (2) Seronegative for hepatitis B virus (HBV) and hepatitis C virus (HCV).
- More than three weeks must have elapsed since any prior systemic therapy at the time of randomization, and patients' toxicities must have recovered to a grade 1 or less (except for alopecia or vitiligo)；
- Normal cardiac ejection fraction and no evidence of pericardial effusion as determined by an echocardiogram；
- More than 30 days must have elapsed since Monoclonal antibody therapy administered prior to apheresis.
Who cannot join
- Patients that require urgent therapy due to tumor mass effects such as bowel obstruction or blood vessel compression；
- Patients that have active hemolytic anemia；
- Patients with detectable cerebrospinal fluid malignant cells or brain metastases or with a history of cerebrospinal fluid malignant cells or brain metastases, or any residual intracranial implants；
- Women of child-bearing potential who are pregnant or breastfeeding；
- Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system；
- Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease)；
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- Concurrent opportunistic infections；
- Concurrent Systemic steroid therapy；
- History of severe immediate hypersensitivity reaction to any of the agents used in this study；
- Patients with central nervous system (CNS) metastases or symptomatic CNS involvement (including cranial neuropathies or mass lesions)；
- CNS-3 disease or traumatic spinal tap with POSITIVE Steinherz/Bleyer algorithm with cerebral spinal fluid involvement with malignancy will make any patient not eligible for this protocol；
- Patients with cardiac atrial or cardiac ventricular lymphoma involvement；
- Other anti-neoplastic investigational agents currently or within 30 days prior to start of the treatment；
- Previous treatment with any gene therapy products.
Trial locations and contacts
1 site in 1 country.
China1 site
Department of Hematology, Dongguan People's Hospital
Dongguan, Guangdong, 523059
About this study
Autologous T cells engineered to express an anti-CD19 chimeric antigen receptor (CAR) will be infused back to patients with B cell malignancies, including lymphoma and leukemia. The patients will be monitored after infusion of anti-CD19 CAR-transduced T cells for adverse events, persistence of anti-CD19 CAR-transduced T cells and treatment efficacy.
Objectives:
Read more
To evaluate the safety and the efficacy of anti-CD19 CAR-transduced T cell therapy for patients with B cell malignancies.
Eligibility:
Patients between 1 and 80 years of age, who have relapsed or refractory CD19-expressing B-cell malignancies (leukemia or lymphoma) that have not responded to standard treatments.
Patients with a history of allogeneic stem cell transplant who meet all eligibility criteria are eligible to participate.
Patients must have adequate organ functions.
Design:
Peripheral blood from patients will be collected for isolation of peripheral blood mononuclear cells (PBMCs), which will be transduced with a lentiviral or retroviral vector encoding anti-CD19 CAR containing a CD28 or 4-1BB and a CD3 zeta as costimulatory domains.
Patients will receive a lymphodepleting preconditioning regimen to prepare their immune system to accept modified T cells.
Patients will receive an infusion of their own modified T cells. They will remain in the hospital to be monitored for adverse events until they have recovered from the treatment.
Patients will have frequent follow-up visits to monitor the persistence of modified T cells and efficacy of the treatment.
Read the detailed description
Despite progress has been made to date in the treatment of patients with B cell malignancies, including leukemia and lymphoma, many patients with relapsed or refractory diseases do not respond to the standard treatments. It has been shown that anti-CD19 CAR-transduced T cells may be an effective approach to treat the relapsed or refractory diseases. The procedure involves collecting PBMCs from the patients and modifying the T cells to attack the malignant B cells. In this trial, autologous T cells engineered to express an anti-CD19 chimeric antigen receptor (CAR) containing the signaling domains of CD28 or 4-1BB and CD3-zeta will be infused back to patients with B cell malignancies, including lymphoma and leukemia. The patients will be pretreated with a lymphodepleting preconditioning regimen before the infusion of anti-CD19 CAR T cells, and will be monitored for adverse events, persistence of anti-CD19 CAR-transduced T cells and the treatment efficacy.
OBJECTIVES:
Primary objectives:
To determine the safety and feasibility of the administration of anti-CD19 CAR transduced T cells in patients with CD19+ B-cell malignancies.
Secondary objectives:
To determine if the treatment regimen can result in clinical regression of B-cell malignancies in the patients as described above.
To determine the in vivo persistency of the anti-CD19 CAR-transduced T cells.
- Being tested
- Drugs and Anti-CD19-CAR transduced T cells
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Drugs and Anti-CD19-CAR transduced T cellsCombination product
Drug: Fludarabine On days -4 through -2, Fludarabine 30mg/m2 IV will be infused over 30 minutes. Drug: Cyclophosphamide On days -4 through -2, Cyclophosphamide 300mg/m2 IV will be infused over 60 minutes followed by fludarabine.
Biological: Anti-CD19-CAR transduced T cells Modified cells will be infused IV over 30 minutes (1-3 days after the last dose of fludarabine).
| Study group | Role | What they receive |
|---|---|---|
| Anti-CD19-CAR transduced T cells | Experimental | Patients will receive a lymphodepleting preconditioning regimen followed by anti-CD19- CAR-transduced T cells.
Interventions:
Drug: Fludarabine Drug: Cyclophosphamide Biological: Anti-CD19-CAR transduced T cells Receives: Combination Product: Drugs and Anti-CD19-CAR transduced T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with Adverse Events
To evaluate the safety and feasibility of the administration of anti-CD19 CAR transduced T cells in patients with CD19+ B-cell malignancies.
Measured: 8 weeks
Secondary outcomes (1)
Number of participants with Clinical responses
To determine if the treatment regimen can result in clinical regression of B-cell malignancies in the patients as described above.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2017
- Study start15 Jan 2016
- Primary completion26 May 2019
- Study completion31 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Lymphocytic LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shenzhen Institute for Innovation and Translational Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Dongguan People's Hospital
- Responsible party
- Sponsor
- Investigators
- Mingjun Wang, MD,PhD, Principal investigator, Shenzhen Institute for Innovation and Translational MedicineYirong Jiang, MD, Principal investigator, Dongguan People's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03076437
- Sponsor's protocol ID
- SIITM20160115
- Status last verified
- Mar 2021
- First submitted
- 7 Mar 2017
- Last updated
- 19 Mar 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Anti-CD19 Chimeric Antigen Receptor (CAR)-Transduced T Cell Therapy for Patients With B Cell Malignancies
- ClinicalTrials.gov ID
- NCT03076437
- Acronym / sponsor ID
- SIITM20160115
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Shenzhen Institute for Innovation and Translational MedicineUniversity, hospital or other
- Collaborators
- Dongguan People's Hospital
- Study start
- 15 Jan 2016 (actual)
- Primary completion
- 26 May 2019 (actual)
- Study completion
- 31 Dec 2019 (actual)
- First posted
- 10 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Autologous T cells engineered to express an anti-CD19 chimeric antigen receptor (CAR) will be infused back to patients with B cell malignancies, including lymphoma and leukemia. The patients will be monitored after infusion of anti-CD19 CAR-transduced T cells for adverse events, persistence of anti-CD19 CAR-transduced T cells and treatment efficacy.
Objectives:
To evaluate the safety and the efficacy of anti-CD19 CAR-transduced T cell therapy for patients with B cell malignancies.
Eligibility:
Patients between 1 and 80 years of age, who have relapsed or refractory CD19-expressing B-cell malignancies (leukemia or lymphoma) that have not responded to standard treatments.
Patients with a history of allogeneic stem cell transplant who meet all eligibility criteria are eligible to participate.
Patients must have adequate organ functions.
Design:
Peripheral blood from patients will be collected for isolation of peripheral blood mononuclear cells (PBMCs), which will be transduced with a lentiviral or retroviral vector encoding anti-CD19 CAR containing a CD28 or 4-1BB and a CD3 zeta as costimulatory domains.
Patients will receive a lymphodepleting preconditioning regimen to prepare their immune system to accept modified T cells.
Patients will receive an infusion of their own modified T cells. They will remain in the hospital to be monitored for adverse events until they have recovered from the treatment.
Patients will have frequent follow-up visits to monitor the persistence of modified T cells and efficacy of the treatment.
Detailed description
Despite progress has been made to date in the treatment of patients with B cell malignancies, including leukemia and lymphoma, many patients with relapsed or refractory diseases do not respond to the standard treatments. It has been shown that anti-CD19 CAR-transduced T cells may be an effective approach to treat the relapsed or refractory diseases. The procedure involves collecting PBMCs from the patients and modifying the T cells to attack the malignant B cells. In this trial, autologous T cells engineered to express an anti-CD19 chimeric antigen receptor (CAR) containing the signaling domains of CD28 or 4-1BB and CD3-zeta will be infused back to patients with B cell malignancies, including lymphoma and leukemia. The patients will be pretreated with a lymphodepleting preconditioning regimen before the infusion of anti-CD19 CAR T cells, and will be monitored for adverse events, persistence of anti-CD19 CAR-transduced T cells and the treatment efficacy.
OBJECTIVES:
Primary objectives:
To determine the safety and feasibility of the administration of anti-CD19 CAR transduced T cells in patients with CD19+ B-cell malignancies.
Secondary objectives:
To determine if the treatment regimen can result in clinical regression of B-cell malignancies in the patients as described above.
To determine the in vivo persistency of the anti-CD19 CAR-transduced T cells.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Anti-CD19-CAR transduced T cells | Experimental | Combination Product: Drugs and Anti-CD19-CAR transduced T cellsPatients will receive a lymphodepleting preconditioning regimen followed by anti-CD19- CAR-transduced T cells. Interventions: Drug: Fludarabine Drug: Cyclophosphamide Biological: Anti-CD19-CAR transduced T cells |
Who may qualify
- Ages
- 1 year to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (16 listed)
- Patients must have a CD19+ B cell malignancy，including relapsed or refractory B cell leukemia and B cell lymphoma；
- Patients with CD19+ B cell malignancies are not able to receive standard treatments and willing to participate in the trial;
- Patients must have a measurable or evaluable disease at the time of enrollment, which may include any evidence of disease including minimal residual disease detected by flow cytometry, cytogenetics, or polymerase chain reaction (PCR) analysis；
- patients are not eligible for autologous or allogeneic stem-cell transplantation (SCT) or relapsed after autologous or allogeneic stem-cell transplantation；
- Patients with history of allogeneic stem cell transplantation are eligible, providing 6 months had elapsed from SCT, they have no evidence of active graft-versus-host disease and no longer taking immunosuppressive agents during the treatment.
Key exclusion criteria (14 listed)
- Patients that require urgent therapy due to tumor mass effects such as bowel obstruction or blood vessel compression；
- Patients that have active hemolytic anemia；
- Patients with detectable cerebrospinal fluid malignant cells or brain metastases or with a history of cerebrospinal fluid malignant cells or brain metastases, or any residual intracranial implants；
- Women of child-bearing potential who are pregnant or breastfeeding；
- Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system；
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Drugs and Anti-CD19-CAR transduced T cellsDrug: Fludarabine On days -4 through -2, Fludarabine 30mg/m2 IV will be infused over 30 minutes. Drug: Cyclophosphamide On days -4 through -2, Cyclophosphamide 300mg/m2 IV will be infused over 60 minutes followed by fludarabine. Biological: Anti-CD19-CAR transduced T cells Modified cells will be infused IV over 30 minutes (1-3 days after the last dose of fludarabine). | Combination product | Anti-CD19-CAR transduced T cells |
Primary outcome
Number of participants with Adverse Events
Time frame: 8 weeks
To evaluate the safety and feasibility of the administration of anti-CD19 CAR transduced T cells in patients with CD19+ B-cell malignancies.
1 secondary outcome
Number of participants with Clinical responses
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mingjun Wang, MD,PhD principal investigator
Shenzhen Institute for Innovation and Translational Medicine
Yirong Jiang, MD principal investigator
Dongguan People's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Drugs and Anti-CD19-CAR transduced T cells in people with Acute Lymphocytic Leukemia and Chronic Lymphocytic Leukemia, run by Shenzhen Institute for Innovation and Translational Medicine at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with Adverse Events (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2021.